Dr. de Jong has prior international research experience and recently completed her clinical training in infectious diseases at Stanford University. In order to foster her transition into an international research scientist, she now proposes to combine didactic training in epidemiology with a hypothesis driven project designed to better understand the determinants of tuberculosis transmission. This work will be conducted in a well-established research setting in the Gambia and mentored by faculty with complementary expertise. Over three consecutive summers she will obtain a Masters degree in epidemiology at the Netherlands Institute for Health Sciences. This curriculum provides a comprehensive survey of the principles and practices of epidemiologic research and is specifically structured to be spread over this period and integrated with an independent research project. The research project that she will pursue tests the hypothesis that genetic differences between mycobacterial strains contribute to variable rates of pulmonary cavitation and person- to- person transmission. It is well established that host and environmental factors greatly impact the clinical manifestations and consequences of infection with M. tuberculosis. However, little is known about the consequences of differences between mycobacterial strains. The combination of expertise the candidate has gained to date working in a molecular epidemiology laboratory and the clinical epidemiologic lessons that she will learn in the classroom will provide her the opportunity to formally address this issue in the field. Specifically, she will spend at least two years in The Gambia quantifying the propensity of clinical isolates of M. tuberculosis to cause cavitation and be transmitted to household contacts. Subsequently, at Stanford University, she will use a DNA microarray based comparative genomic approach to seek genetic correlates of these bacterial propensities. While it would be presumptuous to promise that these activities will have a major impact on the global burden of tuberculosis, it is likely that the proposed project will serve as a vehicle for her transition into an independent physician scientist focused on international translational clinical investigation.